Structure-activity relationships of antifilarial antimycin analogues: a multivariate pattern recognition study.
The structure-activity relationships of a series of novel antifilarial antimycin A1 analogues have been investigated by using computational chemistry and multivariate statistical techniques. The physiochemical descriptors calculated in this way contained information which was useful in the classification of compounds according to their in vitro antifilarial activity. This approach generated a 53 parameter descriptor set, which was reduced with a multivariate pattern recognition package, ARTHUR. Regression analysis of the reduced set yielded several statistically significant regression equations; e.g.-log in vitro activity = 0.017 mp + 0.65 log P - 0.81ESDL10-7.33 (R = 0.9). With use of this equation, it was possible to make predictions for further untested analogues. The analysis indicated that membrane or lipid solubility is an important determinant in biological activity agreeing with the proposed primary mode of action of the compounds as disrupters of cuticular glucose uptake.
Selwood
D L
DL
Wellcome Research Laboratories, Park Langley, Beckenham, Kent, U.K.
Livingstone
D J
DJ
Comley
J C
JC
O'Dowd
A B
AB
Hudson
A T
AT
Jackson
P
P
Jandu
K S
KS
Rose
V S
VS
Stables
J N
JN
D000818:Animals; D000871:Anthelmintics; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D003198:Computer Simulation; D006224:Cricetinae; D004153:Dipetalonema / Q000187:drug effects; D004154:Dipetalonema Infections / Q000188:drug therapy; D004605:Elephantiasis, Filarial / Q000188:drug therapy; D005260:Female; D005369:Filaricides; D005849:Gerbillinae; D008297:Male; D015394:Molecular Structure; D015999:Multivariate Analysis; D012044:Regression Analysis; D013329:Structure-Activity Relationship
D000871:Anthelmintics; D005369:Filaricides; D000968:Antimycin A